Medical Genetics Commons^™

Department Of Pathology, Thomas Jefferson University, Identification Of Conserved Gene Expression Features Between Murine Mammary Carcinoma Models And Human Breast Tumors., Jason I Herschkowitz, Karl Simin, Victor J Weigman, Igor Mikaelian, Jerry Usary, Zhiyuan Hu, Karen E Rasmussen, Laundette P Jones, Shahin Assefnia, Subhashini Chandrasekharan, Michael G Backlund, Yuzhi Yin, Andrey I Khramtsov, Roy Bastein, John Quackenbush, Robert I Glazer, Powel H Brown, Jeffrey E Green, Levy Kopelovich, Priscilla A Furth, Juan P Palazzo, Olufunmilayo I Olopade, Philip S Bernard, Gary A Churchill, Terry Van Dyke, Charles M Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of …

Up-Regulation Of Interferon-A/Apobec3g Signal Pathway Potently Inactivates Hiv-1 Infectivity In Resting Cd4-T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Giuseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

Poster Presentation.

Chemoprevention Of Breast Cancer For Women At Hgh Risk, Kathryn Chan, Gloria J. Morris

Department of Medicine Faculty Papers

Breast cancer remains the second most common cause of cancer death in the United States. Several studies have identified cohorts of women at higher than average risk to develop this disease. These are women who are exposed to high levels of endogenous or exogenous estrogens, those with a family history of breast cancer, and those who harbor benign breast disease or genetic mutations that predispose to breast cancer. In this population group, adapting a chemoprevention strategy to decrease the risk of developing overt disease is a strong consideration. To this end, tamoxifen is the most accepted agent to date. This …

Donor Tricuspid Annuloplasty During Orthotopic Heart Transplantation: Long-Term Results Of A Prospective Controlled Study, Valluvan Jeevanandum, Hyde Russell, Paul Mather, Satoshi Furukawa, Allen Anderson, Jaishankar Raman

Department of Medicine Faculty Papers

Background: Development of tricuspid regurgitation after orthotopic heart transplantation can cause heart failure along with renal and hepatic impairment and portends a poor prognosis. If tricuspid regurgitation causes significant symptoms, tricuspid valve repair or replacement is often required. This study was designed to study the effects of prophylactic tricuspid valve annuloplasty (TVA) during orthotopic heart transplantation on long-term survival, renal function, and amount of tricuspid regurgitation.

Methods: Between April 1997 and March 1998, 60 patients (aged 18 to 70 years; 22 female) randomly received either standard bicaval orthotopic heart transplantation (group STD; n = 30) or bicaval orthotopic …

Antimicrobial Effects Of Liquid Anesthetic Isoflurane On Candida Albicans, Viachaslau M. Barodka, Edward Acheampong, Garry Powell, Ludmilla Lobach, David A. Logan, Zahida Parveen, Valerie Armstead, Muhammad Mukhtar

Department of Medicine Faculty Papers

Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections …

Hydroxyurea And Sickle Cell Anemia: Effect On Quality Of Life, Samir K. Ballas, Franca B. Barton, Myron K. Waclawiw, Paul Swerdlow, James R. Eckman, Charles H. Pegelow, Mabel Koshy, Bruce A. Barton, Duane R. Bonds

Department of Medicine Faculty Papers

Background: The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals.

Methods: The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of life (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit …

Case Report: Sigmoid Schwannoma As The Lead Point For Intussusception In An Adult Patient With Neurofibromatosis, Roger Coron, Herve Boucard, Robert Richards

Department of Medicine Faculty Papers

No abstract available.

Alpha Interferon Potently Enhances The Anti-Human Immunodeficiency Virus Type 1 Activity Of Apobec3g In Resting Primary Cd4 T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Guiseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-{alpha}/ß signal transduction pathway, IFN-{alpha} can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting …

Rho Kinase As A Novel Molecular Therapeutic Target For Hypertensive Internal Anal Sphincter, Satish Rattan, Marcio A.F. De Godoy, Chirag A. Patel

Department of Medicine Faculty Papers

Background & Aims: An increase in Rho kinase (ROK) activity has been associated with the agonist-induced sustained contraction of the smooth muscle, but its role in the pathophysiology of spontaneously tonic smooth muscle is not known.

Methods: Present studies examined the effects of ROK inhibitor Y 27632 in the tonic smooth muscle of the rat internal anal sphincter (IAS) vs. in the flanking phasic smooth muscle of the rectum (RSM). In addition, studies were performed to determine the relationship between the decreases in the basal IAS tone vs. the ROK activity. Confocal microscopic studies determined the cellular distribution of smooth …

Endoscopic Sphincterotomy With Or Without Cholecystectomy For Choledocholithiasis In High Risk Surgical Patients: A Decision Analysis, Ali Siddiqui, Pradnya Mitroo, Thomas E. Kowalski, David Loren

Department of Medicine Faculty Papers

Background

Laparoscopic cholecystectomy (LC) is recommended for patients with choledocholithiasis after ERCP with sphincterotomy (ES) and stone extraction.

Aim: We designed a decision model to address whether ES alone versus ES followed by LC (ES + LC) is the optimal treatment in high-risk patients with choledocholithiasis.

Methods:

Our cohort were patients with obstructive jaundice who have undergone an ES with biliary clearance. Recurrent biliary complications over a 2-year period stratified by gallbladder status (in/out) and age-stratified surgical complication rates were obtained from the literature. Failure of therapy was defined as either recurrent symptoms or death attributed to biliary complications.

Results …

Gαq And Its AktIons, David M. Harris, Andrea D. Eckhart, Walter J. Koch

Department of Medicine Faculty Papers

No abstract available.

Alterations In Vasodilator-Stimulated Phosphoprotein (Vasp) Phosphorylation: Associations With Asthmatic Phenotype, Airway Inflammation And Β2-Agonist Use, Annette T. Hastie, Min Wu, Gayle C. Foster, Gregory A. Hawkins, Vikas Batra, Katherine A. Rybinski, Rosemary Cirelli, James G. Zangrilli, Stephen P. Peters

Department of Medicine Faculty Papers

Background

Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β₂-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion.

Methods

Bronchial epithelium was obtained from asthmatic …

Clinical Perspectives Of Emerging Pathogens In Bleeding Disorders, Jamie Siegel

Department of Medicine Faculty Papers

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be …

Characterization Of Hard2, A Processed Hard1 Gene Duplicate, Encoding A Human Protein N-Alpha-Acetyltransferase., Thomas Arnesen, Matthew J Betts, Frédéric Pendino, David A Liberles, Dave Anderson, Jaime Caro, Xianguo Kong, Jan E Varhaug, Johan R Lillehaug

Department of Medicine Faculty Papers

BACKGROUND: Protein acetylation is increasingly recognized as an important mechanism regulating a variety of cellular functions. Several human protein acetyltransferases have been characterized, most of them catalyzing epsilon-acetylation of histones and transcription factors. We recently described the human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N-terminal alpha-acetylation activity. RESULTS: We here describe a human protein, hARD2, with 81 % sequence identity to hARD1. The gene encoding hARD2 most likely originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA and protein are expressed in several human cell lines. …

Orally Delivered, Plant-Produced Tat Protein Primes Mice For A Challenge Dna Vaccine Expressing Tat, A V. Karasev, S Foulke, C Wellens, I Zwierzynski, R Baldwin, H Koprowski, M S. Reitz Jr

Department of Microbiology and Immunology Faculty Papers

Oral Presentation.

Mammalian Micrornas: A Small World For Fine-Tuning Gene Expression, Cinzia Sevignani, George A. Calin, Linda D. Siracusa, Carlo M. Croce

Department of Microbiology and Immunology Faculty Papers

The basis of eukaryotic complexity is an intricate genetic architecture where parallel systems are involved in tuning gene expression, via RNA-DNA, RNA-RNA and RNA-protein and DNA-protein interactions. In higher organisms, about 97% of the transcriptional output is represented by non-coding RNA (ncRNA) encompassing not only rRNA, tRNA, introns, 5’ and 3’-untranslated regions, transposable elements and intergenic regions, but also a large rapidly emerging family, named microRNAs. MicroRNAs are short 20-22 nucleotide RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. MicroRNAs are formed from larger transcripts that fold to produce …

Two-Dimensional Fluorescence Difference Gel Electrophoresis Analysis Of The Urine Proteome In Human Diabetic Nephropathy, Kumar Sharma, Sohee Lee, Steven Han, Sungchun Lee, Barbara Francos, Peter Mccue, Richard Wassell, M. Alexander Shaw, Satish P. Ramachandrarao

Department of Medicine Faculty Papers

Urinary proteins may provide clues regarding pathogenesis of kidney disease as well as providing markers of disease activity. We employed two-dimensional differential in-gel electrophoretic analysis (2-D DIGE) to assess multiple urine samples in patients with diabetic nephropathy. Patient samples were collected as timed overnight collections. All the patients had longstanding diabetes, impaired renal function, and overt proteinuria. Control and patient urinary protein were analyzed by 2-D DIGE and DeCyder analysis. Ninety-nine spots were significantly regulated in the urine proteome of the diabetic samples, with 63 up- and 36 down-regulated. One spot corresponding to a pI 5–6 and a molecular weight …

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy, Katalin Susztack, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin Böttinger

Department of Medicine Faculty Papers

Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …

Global Gene Expression Profiling Of Cells Overexpressing Smc3., Giancarlo Ghiselli, Chang-Gong Liu

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. RESULTS: Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization …

Characterization Of The Chicken Inward Rectifier K+ Channel Irk1/Kir2.1 Gene., Hideki Mutai, Lawrence C Kenyon, Emily Locke, Nami Kikuchi, John Carl Oberholtzer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Inward rectifier potassium channels (IRK) contribute to the normal function of skeletal and cardiac muscle cells. The chick inward rectifier K+ channel cIRK1/Kir2.1 is expressed in skeletal muscle, heart, brain, but not in liver; a distribution similar but not identical to that of mouse Kir2.1. We set out to explore regulatory domains of the cIRK1 promoter that enhance or inhibit expression of the gene in different cell types. RESULTS: We cloned and characterized the 5'-flanking region of cIRK1. cIRK1 contains two exons with splice sites in the 5'-untranslated region, a structure similar to mouse and human orthologs. cIRK1 has …

Heme Oxygenase-2 Gene Deletion Attenuates Oxidative Stress In Neurons Exposed To Extracellular Hemin., Raymond F Regan, Jing Chen, Luna Benvenisti-Zarom

Department of Emergency Medicine Faculty Papers

BACKGROUND: Hemin, the oxidized form of heme, accumulates in intracranial hematomas and is a potent oxidant. Growing evidence suggests that it contributes to delayed injury to surrounding tissue, and that this process is affected by the heme oxygenase enzymes. In a prior study, heme oxygenase-2 gene deletion increased the vulnerability of cultured cortical astrocytes to hemin. The present study tested the effect of HO-2 gene deletion on protein oxidation, reactive oxygen species formation, and cell viability after mixed cortical neuron/astrocyte cultures were incubated with neurotoxic concentrations of hemin. RESULTS: Continuous exposure of wild-type cultures to 1-10 microM hemin for 14 …

Durable Cytotoxic Immune Responses Against Gp120 Elicited By Recombinant Sv40 Vectors Encoding Hiv-1 Gp120 +/- Il-15., Hayley J Mckee, Patricia Y T'Sao, Maria Vera, Puri Fortes, David S Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: A vaccine that elicits durable, powerful anti-HIV immunity remains an elusive goal. In these studies we tested whether multiple treatments with viral vector-delivered HIV envelope antigen (gp120), with and without IL-15, could help to approach that goal. For this purpose, we used recombinant Tag-deleted SV40-derived vectors (rSV40s), since they do not elicit neutralizing antibody responses, and so can be given multiply without loss of transduction efficiency. METHODS: SV(gp120) carried the coding sequences for HIV-1NL4-3 Env, and SV(mIL-15) carried the cDNA for mouse IL-15. Singly, and in combination, these two vectors were given monthly to BALB/cJ mice. Cytotoxic immunity and …

The Nad(P)H Oxidase Homolog Nox4 Modulates Insulin-Stimulated Generation Of H202 And Plays An Integral Role In Insulin Signal Transduction, Kalyankar Mahadev, Hiroyuki Motoshima, Xiangdong Wu, Jean Marie Ruddy, Rebecca S. Arnold, Guangjie Cheng, J. David Lambeth, Barry J. Goldstein

Department of Medicine Faculty Papers

Insulin stimulation of target cells elicits a burst of H₂O₂ that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative …

Signaling And Regulation Of G Protein-Coupled Receptors In Airway Smooth Muscle., Charlotte K Billington, Raymond B Penn

Department of Medicine Faculty Papers

Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the …

High-Resolution Physical Map For Chromosome 16q12.1-Q13, The Blau Syndrome Locus., Xiaoju Wang, Helena Kuivaniemi, Gina Bonavita, Charlene J Williams, Gerard Tromp

Department of Medicine Faculty Papers

BACKGROUND: The Blau syndrome (MIM 186580), an autosomal dominant granulomatous disease, was previously mapped to chromosome 16p12-q21. However, inconsistent physical maps of the region and consequently an unknown order of microsatellite markers, hampered us from further refining the genetic locus for the Blau syndrome. To address this problem, we constructed our own high-resolution physical map for the Blau susceptibility region. RESULTS: We generated a high-resolution physical map that provides more than 90% coverage of a refined Blau susceptibility region. The map consists of four contigs of sequence tagged site-based bacterial artificial chromosomes with a total of 124 bacterial artificial chromosomes, …

Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein alpha subunit, has been shown to produce an additional protein, termed salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found predominantly at cellular plasma membranes, salpha(i2) has been localized to intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have been suggested to constitute a specific targeting signal. RESULTS: This paper proposes and examines an alternative hypothesis: disruption of the normal C-terminus of alpha(i2) produces an unstable protein that fails to localize to plasma …

Association Of Ace Polymorphism And Diabetic Nephropathy In South Indian Patients, Vijay Viswanathan, Yanqing Zhu, Karthik Bala, Stephen Dunn, Chamukuttan Snehalatha, Ambady Ramachandran, Muthu Jayaraman, Kumar Sharma

Department of Medicine Faculty Papers

Objective: To study the association of ACE gene polymorphism and diabetic nephropathy in South Indian subjects.

Setting: Outpatient clinic of a specialized hospital.

Patients: The study included 109 South Indian type 2 diabetic patients (72 males and 37 females; age 56.7±9.0 years, mean±SD). The patients were subdivided into two groups: nephropathic (n=86) and normoalbuminuric patients (n=23).

Interventions: Genomic DNA was isolated from the peripheral blood leukocytes. To determine the ACE genotype, genomic DNA was amplified by PCR initially using a flanking primer pair and, subsequently when necessary, with a primer pair that recognizes the insertion specific sequence for confirmation of …

Technology Evaluation: Pro-542, Progenics Pharmaceuticals Inc., Muhammad Mukhtar, Zahida Parveen, Roger J Pomerantz

Department of Medicine Faculty Papers

Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the …

Long-Term Prevention Of Renal Insufficiency, Excess Matrix Gene Expression, And Glomerular Mesangial Matrix Expansion By Treatment With Monoclonal Antitransforming Growth Factor-Ss Antibody In Db/Db Diabetic Mice , Fuad N. Ziyadeh, Brenda B. Hoffman, Dong Cheol Han, M. Carmen Iglesias-De La Cruz, Soon Won Hong, Motohide Isono, Sheldon Chen, Tracy A. Mcgowan, Kumar Sharma

Department of Medicine Faculty Papers

Emerging evidence suggests that transforming growth factor-(TGF-β) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-antibody (αT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of αT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with α or control IgG, …